L-deprenyl is a selective monoamine oxidase B (MAO-B) inhibitor, which is widely used as an adjunct in the treatment of Parkinson's disease. While its most common usage is for the treatment of Parkinson's disease, L-deprenyl was originally developed as an antidepressant agent. Recent testing has indicated that L-deprenyl may have some effect on increasing sexual response in aging animals, and also may have some effect, at least in rats in increasing life expectancy. However, to date L-deprenyl has only been medically approved by regulatory agencies for use as a treatment for Parkinson's disease in humans.
Parkinson's disease is a distinct disease associated with depletion of dopamine in the basal ganglia area of the brain, and the cardinal signs relate to motor dysfunction. Parkinson's disease is one of the most common causes of disability in older humans, with approximately 1% of persons being afflicted after age 60 (Jankovic, J. Parkinsonism. In: Conn's Current Therapy 1992; R. Rakel (ed.), W. B. Saunders Co., page 880, 1992). The cardinal signs involve various motor deficits, sometimes complicated by either neurobehavioral or other non-motor problems. Typical pathologic lesions of Parkinson's disease include neuronal "dropout" and the presence of Lewey bodies in the substantia nigra. The disease is considered progressive, despite advances in therapy. L-dopa replacement therapy is the primary medical treatment, although l-deprenyl and anticholinergics are also used in Parkinson's disease therapy.
Parkinson's disease is normally not thought of as a disease of immune system dysfunction although there are some literature reports discussing immune system abnormalities in Parkinson's disease. However, many Parkinson's Disease patients do show quite normal immune system function. Furthermore, there are no known reports of using l-deprenyl to treat immune system abnormalities. The limited reports of immune system dysfunction in Parkinsonians have been inconsistent, and tend to identify immune system problems in chronically PD-afflicted persons, the same persons who have received extended therapy with l-dopa. It is known that l-dopa may cause T-lymphocyte functional abnormalities in mice (Boukhris, W., Kouassi, E. et al. Impaired T-Dependent Immune Response in L-Dopa Treated BALB/C Mice. J. Clin. Lab. Immunol. 23(4). p. 185-189, 1987). Thus, the immune system abnormalities seen in some cases of PD may be caused by chronic l-dopa therapy. Since l-deprenyl is used to augment l-dopa therapy, it would be reasonable to conclude that l-deprenyl therapy would increase rather than decrease any immune system abnormalities in PD. To our knowledge, there are no published reports discussing l-deprenyl and its effect on the immune system function in either health or disease states, and there are no published reports describing the treatment of immune system dysfunction in any species with l-deprenyl.
Immune system dysfunction can and does occur at any stage of life due to a variety of causes, including aging (see p. 10-13). In many animals, i.e., man, dogs, monkeys, etc., immune system dysfunction, particularly as the animal ages, can substantially increase disease risk, which can threaten life itself. It is therefore important for over all well being to effectively treat any immune system dysfunction. Doing so will retard the risk of diseases known to affect animals with lowered immune response.
There is, therefore, a continuing and real need for the development of medications which treat immune system dysfunction.
In the grandparent application of co-inventor Milgram, now U.S. Pat. No. 5,151,449, there are disclosed certain uses of L-deprenyl for retardation of normal age dependent deterioration of renal function, retardation of normal degeneration of cognitive abilities, and for retardation of age dependent weight loss. In accordance with the improvement invention of parent application 07/643,452, it had been discovered that L-deprenyl will also assist in maintenance of thyroid function, adrenal function, immune system function and maintenance of body composition in aging mammals, providing that certain doses and levels of use were maintained. It may also be useful in treating Cushing's disease, (see Ruehl, Therapeutic Effect of L-Deprenyl In The Management of Pituitary-Dependant Hyperadrenocorticism (Cushing's Disease) filed Mar. 27, 1992).
While L-deprenyl is a known compound, it has never before been demonstrated effective and used at any level to treat immune system dysfunction.
Like most drugs, L-deprenyl can have diverse physiological effects which are completely dependent upon the dose administered. In accordance with the present invention, L-deprenyl can be used for successful methods of treatment for immune system dysfunction, providing that it is used at the dosage levels mentioned herein, and providing it is administered at the periodic intervals and for the length of time mentioned herein. Obviously, when different dosages and levels of treatment are used, the results expressed herein may not be achieved. In fact, at higher doses, adverse behavioral effects may be encountered.
Accordingly, a primary objective of the present invention is to develop a dosage regimen for use of L-deprenyl to treat immune system dysfunction in mammals.
The method and means of accomplishing this as well as other primary objectives of the present invention will be apparent from the detailed description which will follow hereinafter.